Zymogen Activation by Proteolytic Cleavage

Insulin associated with amino acids

-Insulin is secreted from the pancreas not only in response to high serum glucose but also by high serum AA, especially Leu

-Insulin stimulates not only storage of glucose and fatty acids but also synthesis of proteins

Aminotransferases

-catalyze the transfer of a-amino groups of amino acids to a-ketoglutarate

-Pyridoxal phosphate (PLP) is the co-factor required by aminotransferases

-PLP is derived from vitamin B6

The amino group converts PLP to pyridoxamine phosphate

glutamate dehydrogenase (GDH)

- catalyzes the reaction  of Glu releasing  its amino group  as ammonia in the liver

glutamine synthetase

-Gln transports ammonia in the bloodstream to the liver

-•Gln is synthesized by glutamine synthetase

carbamoyl phosphate synthetase I    (CPS I)

-Occurs in the mitochondrion (CPS II is cytosolic and is for pyrimidine biosynthesis)

-Requires hydrolysis of two ~P of ATP

-CPS I requires  N-acetylgluatmate (NAG) as an  allosteric activator

ornithine transcarbamoylase (OTC)

- catalyzes condensation of carbamoyl phosphate with ornithine to yield citrulline

-Occurs in the mitochondrion

-Citrulline is then exported from the mitochondrion to the cytosol

argininosuccinate synthetase

-catalyzes condensation of Asp with the ureido group of citrulline to form argininosuccinate

-The second N enters here

-Requires ATP to activate the citrulline ureido group

-Both high energy phosphate bonds of ATP are used because the released PPi is cleaved to Pi

argininosuccinase

-Argininosuccinate is cleaved to fumarate and Arg

-Fumarate can enter the mitochondrion via conversion to malate Arg remains in the cytosol for the last reaction of the cycle

arginase

- catalyzes cleavage of Arg to urea an ornithine

-Urea is exported from the cell to the blood, destined for the kidney

Ornithine re-enters the mitochondrion for another round of the cycle